scholarly journals Possible contribution of trained immunity in faulty hormonal imprinting and DOHaD: Review and hypothesis

2020 ◽  
Author(s):  
György Csaba
Keyword(s):  
Animal Experiments ◽  
Innate Immune ◽  
Immune Memory ◽  
Early Adversity ◽  
Hormonal Imprinting ◽  
Adult Age ◽  
Adaptive Immune ◽  
Base Sequences ◽  
Long Time ◽  
Health And Disease

AbstractThe faulty hormonal imprinting theory (published in 1980) and the DOHaD (Developmental Origin of Health and Disease theory (published in 1986) are twin-concepts: both justify the manifestation after long time (in adults) diseases which had been provoked in differentiating cells (e.g. during gestation). This was demonstrated using animal experiments as well, as comparative statistical methods (in human cases). However, there is no explanation for the tools of memorization (even after decades) of the early adversity and the tools of execution (manifestation) in adult age. It seems likely that immune memory is involved to the memorization of early adversity, up to the manifestation of the result (non-communicable diseases). Nevertheless, the relatively short timespan of adaptive immune memory makes this system insuitable for this function, however the newly recognized trained memory of the innate immune system seems to be theoretically suitable for the storage of the records and handling the sequalae, which is the epigenetic reprogramming in the time of provocation, without changes in base sequences (mutation). The flawed (damaged) program is manifested later, in adult age. Evidences are incomplete, so further animal experiments and human observations are needed for justifying the theory.

scholarly journals Trained Immunity at a Glance; A Review on the Innate Immune Memory and its Potential Role in Infections, Diseases and New Therapeutic Strategies

2020 ◽  
Vol 8 (1) ◽  
pp. 68-81
Author(s):  
Silvia Incalcaterra ◽  
Jorge Andres Dominguez
Keyword(s):  
Therapeutic Strategies ◽  
Innate Immune ◽  
Immune Memory ◽  
Therapeutic Approaches ◽  
Trained Immunity ◽  
Adaptive Immune ◽  
Specific Memory ◽  
Health And Disease ◽  
The Impact ◽  
Infections Diseases

Despite the existence of two different branches of immunity, innate and adaptive, it has been described that both systems are characterized by the establishment of memory responses. Indeed, it has been shown that cells belonging to the innate immune system can express a so-called “trained” memory, although it has different features from the adaptive immune memory. Adaptive memory is a long-lasting specific memory whereas innate memory involves non-specific responses which enhance the immune response during a second reinfection. However, many aspects of the trained immunity are still unclear. Metabolic and epigenetic reprogramming have been pointed as the two processes responsible for the establishment of the innate memory. Trained immunity seems to be responsible for the heterologous effect of many vaccines such as BCG, thus giving insights for the development of new therapies. Although its potential beneficial role, trained immunity could also have detrimental effects that might worsen the progress of certain diseases. The purpose of this literature review is to provide an in-depth review on the major characteristics of trained immunity, describing the main pathways at the basis of the evolution and establishment of memory in innate cells. In addition, the present review assesses the modern evidence of the impact of trained immunity in health and disease, strengthening the hypotheses that this innate memory may be considered both in the formulation of new therapeutic strategies and in the current therapeutic approaches.

Bone Manifestation of Faulty Perinatal Hormonal Imprinting: A Review

2019 ◽  
Vol 15 (1) ◽  
pp. 4-9
Author(s):  
G. Csaba
Keyword(s):  
Animal Behavior ◽  
Binding Capacity ◽  
Animal Experiments ◽  
Osteoporotic Fractures ◽  
Postnatal Period ◽  
Hormonal Imprinting ◽  
Adult Age ◽  
Pathological Development ◽  
Synthetic Hormones ◽  
Critical Developmental Period

Hormonal imprinting takes place at the first encounter between the developing receptor and its target hormone and the encounter determines the receptor's binding capacity for life. In the critical period of development, when the window for imprinting is open, the receptor can be misdirected by related hormones, synthetic hormones, and industrial or communal endocrine disruptors which cause faulty hormonal imprinting with life-long consequences. Considering these facts, the hormonal imprinting is a functional teratogen provoking alterations in the perinatal (early postnatal) period. One single encounter with a low dose of the imprinter in the critical developmental period is enough for the formation of faulty imprinting, which is manifested later, in adult age. This has been justified in the immune system, in sexuality, in animal behavior and brain neurotransmitters etc. by animal experiments and human observations. This review points to the faulty hormonal imprinting in the case of bones (skeleton), by single or repeated treatments. The imprinting is an epigenetic alteration which is inherited to the progeny generations. From clinical aspect, the faulty imprinting can have a role in the pathological development of the bones as well, as in the risk of osteoporotic fractures, etc.

scholarly journals The Role of Cell Metabolism in Innate Immune Memory

2020 ◽  
pp. 1-9
Author(s):  
Anaisa Valido Ferreira ◽  
Jorge Domiguéz-Andrés ◽  
Mihai Gheorghe Netea
Keyword(s):  
Metabolic Pathways ◽  
Tricarboxylic Acid Cycle ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Immune Memory ◽  
Functional Changes ◽  
Trained Immunity ◽  
Health And Disease

Immunological memory is classically attributed to adaptive immune responses, but recent studies have shown that challenged innate immune cells can display long-term functional changes that increase nonspecific responsiveness to subsequent infections. This phenomenon, coined <i>trained immunity</i> or <i>innate immune memory</i>, is based on the epigenetic reprogramming and the rewiring of intracellular metabolic pathways. Here, we review the different metabolic pathways that are modulated in trained immunity. Glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, amino acid, and lipid metabolism are interplaying pathways that are crucial for the establishment of innate immune memory. Unraveling this metabolic wiring allows for a better understanding of innate immune contribution to health and disease. These insights may open avenues for the development of future therapies that aim to harness or dampen the power of the innate immune response.

scholarly journals Trained immunity: A program of innate immune memory in health and disease

Science ◽  
2016 ◽  
Vol 352 (6284) ◽  
pp. aaf1098-aaf1098 ◽  
Author(s):  
M. G. Netea ◽  
L. A. B. Joosten ◽  
E. Latz ◽  
K. H. G. Mills ◽  
G. Natoli ◽  
...  
Keyword(s):  
Innate Immune ◽  
Immune Memory ◽  
Trained Immunity ◽  
Health And Disease

scholarly journals The Neutrophil’s Role During Health and Disease

2019 ◽  
Vol 99 (2) ◽  
pp. 1223-1248 ◽  
Author(s):  
Pei Xiong Liew ◽  
Paul Kubes
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Acute Injury ◽  
Complex Cells ◽  
Adaptive Immune ◽  
Inflammatory Processes ◽  
Health And Disease ◽  
Injury And Repair

Neutrophils have always been considered as uncomplicated front-line troopers of the innate immune system equipped with limited proinflammatory duties. Yet recently, the role of the neutrophil has been undergoing a rejuvenation of sorts. Neutrophils are now considered complex cells capable of a significant array of specialized functions, and as an effector of the innate immune response, they are able to regulate many processes such as acute injury and repair, cancer, autoimmunity, and chronic inflammatory processes. Furthermore, evidence exists to indicate that neutrophils also contribute to adaptive immunity by aiding the development of specific adaptive immune responses or guiding the subsequent adaptive immune response. With this revived interest in neutrophils and their many novel functions, it is prudent to review what is currently known about neutrophils and, even more importantly, understand what information is lacking. We discuss the essential features of the neutrophil, from its origins, lifespan, subsets, margination and sequestration of the neutrophil to the death of the neutrophil. We highlight neutrophil recruitment to both infected and injured tissues and outline differences in recruitment of neutrophils between different tissues. Finally, we examine how neutrophils use different mechanisms to either bolster protective immune responses or negatively cause pathological outcomes at different locations.

scholarly journals The right microbial stimulus can direct innate immune effector cells to specific organ sites to clear pathology

2019 ◽  
Author(s):  
Shirin Kalyan ◽  
Mark Bazett ◽  
Ho Pan Sham ◽  
Momir Bosiljcic ◽  
Beryl Luk ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune ◽  
Immune Memory ◽  
Immune Effector ◽  
Effector Cells ◽  
Adaptive Immune ◽  
Immune Effector Cells ◽  
Innate Immune Effector ◽  
Organ Site ◽  
Tissue Site

ABSTRACTRecent developments in understanding how the functional phenotype of the innate immune system is programmed has led to paradigm-shifting views on immunomodulation. These advances have overturned two long-held dogmas: only adaptive immunity confers immunological memory and innate immunity lacks specificity. This work describes the novel observation that innate immune effector cells can be recruited to specific tissues of the body where pathology is present by using a microbial-based immune stimulus that consists of an inactivated pathogen that typically resides or causes infection in that target tissue site. We demonstrate this principle using experimental models of cancer and infection for which different subcutaneously delivered microbial-based treatments were shown to induce the recruitment of immune effector cells to specific diseased organs. Amelioration of disease in a given organ niche was dependent on matching the correct microbial stimulus for the affected organ site but was independent of the nature of the pathology. This observation intriguingly suggests that the immune system, upon pathogen recognition, tends to direct its resources to the compartment in which the pathogen has previously been encountered and would be the most likely source of infection. Importantly, this phenomenon provides a novel means to therapeutically target innate immune effector cells to sites of specific disease localization to potentially treat a wide spectrum of pathologies, including cancer, infection, and chronic inflammatory disorders.AUTHOR SUMMARYVaccines that target adaptive immune memory have revolutionized medicine. This study describes a novel strategy that works as a modified innate immune “vaccine” that exploits the trained response of innate immune effector cells to clear pathology in a specific tissue site. Unlike memory of the adaptive immune system, which functions like a lock and key, innate immune memory is more akin to a reflex response – like experienced muscle or neural cells that are changed by a stimulus to respond more efficiently upon re-exposure. This change in behavior through experience is the definition of learning. Our study suggests that this innate immune learning occurs at different levels. Emergency hematopoiesis trains new innate immune cells in the bone marrow to respond quickly and effectively to a non-specific threat; whereas, pathogen-specific training occurs at sites where cells making up the immunologic niche have had interactions with a particular pathogen and have been trained to respond more robustly to it upon re-presentation in the context of a danger signal. The speed with which new immune cells are trained in the bone marrow in response to an imminent microbial threat and their subsequent recruitment to the target organ site where that microbe typically resides suggests there are ways the immune system communicates to coordinate this rapid response that are yet to be fully delineated. These findings provide a novel highly proficient way to harness the potent effector functions of the innate immune system to address a wide range of immune-based diseases.

Trained Immunity: Reprogramming Innate Immunity in Health and Disease

2021 ◽  
Vol 39 (1) ◽  
pp. 667-693 ◽  
Author(s):  
Siroon Bekkering ◽  
Jorge Domínguez-Andrés ◽  
Leo A.B. Joosten ◽  
Niels P. Riksen ◽  
Mihai G. Netea
Keyword(s):  
Innate Immune ◽  
Autoinflammatory Syndromes ◽  
Trained Immunity ◽  
Adaptive Immune ◽  
Inflammatory Conditions ◽  
Current State ◽  
Secondary Infections ◽  
Health And Disease ◽  
Adaptive Immune Systems ◽  
Memory Characteristics

Traditionally, the innate and adaptive immune systems are differentiated by their specificity and memory capacity. In recent years, however, this paradigm has shifted: Cells of the innate immune system appear to be able to gain memory characteristics after transient stimulation, resulting in an enhanced response upon secondary challenge. This phenomenon has been called trained immunity. Trained immunity is characterized by nonspecific increased responsiveness, mediated via extensive metabolic and epigenetic reprogramming. Trained immunity explains the heterologous effects of vaccines, which result in increased protection against secondary infections. However, in chronic inflammatory conditions, trained immunity can induce maladaptive effects and contribute to hyperinflammation and progression of cardiovascular disease, autoinflammatory syndromes, and neuroinflammation. In this review we summarize the current state of the field of trained immunity, its mechanisms, and its roles in both health and disease.

Immunological Mechanism and Clinical Application of PAMP Adjuvants

2021 ◽  
Vol 16 ◽  
Author(s):  
Yu Yan ◽  
Dan Yao ◽  
Xiaoyu Li
Keyword(s):  
Immune Responses ◽  
Tumor Therapy ◽  
Clinical Applications ◽  
Innate Immune ◽  
Research Progress ◽  
Immune Memory ◽  
Adaptive Immune Responses ◽  
Immunological Mechanism ◽  
Immune Mechanisms ◽  
Adaptive Immune

Background: The host innate immune system can recognize Pathogen-Associated Molecular Patterns (PAMPs) through Pattern Recognition Receptors (PRRs), thereby initiating innate immune responses and subsequent adaptive immune responses. PAMPs can be developed as a vaccine adjuvant for modulating and optimizing antigen-specific immune responses, especially in combating viral infections and tumor therapy. Although several PAMP adjuvants have been successfully developed, they are still lacking in general, and many are in the preclinical exploration stage. Objective: This review summarizes the research progress and development direction of PAMP adjuvants, focusing on their immune mechanisms and clinical applications. Methods: PubMed, Scopus, and Google Scholar were screened for this information. We highlight the immune mechanisms and clinical applications of PAMP adjuvants. Results: Because of the differences in receptor positions, specific immune cells targets, and signaling pathways, the detailed molecular mechanism and pharmacokinetic properties of one agonist cannot be fully generalized to another agonist, and each PAMP should be studied separately. In addition, combination therapy and effective integration of different adjuvants can increase the additional efficacy of innate and adaptive immune responses. Conclusion: The mechanisms by which PAMPs exert adjuvant functions are diverse. With continuous discovery in the future, constant adjustments should be made to build new understandings. At present, the goal of therapeutic vaccination is to induce T cells that can specifically recognize and eliminate tumor cells and establish long-term immune memory. Following immune checkpoint modulation therapy, cancer treatment vaccines may be an option worthy of clinical testing.

scholarly journals Rigidity of Cell Fate and Function Among Monocytes

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2057-2057
Author(s):  
Catherine Rhee ◽  
Elizabeth W Scadden ◽  
Lai Ping Wong ◽  
Giulia Schiroli ◽  
Michael Mazzola ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Board Of Directors ◽  
Myeloid Cells ◽  
Innate Immune ◽  
Immune Memory ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Adaptive Immune ◽  
Classical Monocytes ◽  
Privately Held

Abstract Myeloid cells are the most evolutionarily ancient aspect of a specialized immune system and the cornerstone of innate immunity in vertebrates. Innate immunity serves at the front line of host defense playing essential roles in directly clearing infection while also activating adaptive immune cell populations. Even with the importance in its roles, the myeloid system has often been regarded as the 'dumb brute' side of cell-based immunity with limited specificity and variability of responses. Heterogeneity in innate immune cells is increasingly recognized but still modest compared to other cell types and constrained by limited investigative tools. Monocytes have traditionally been categorized into two subsets: classical and non-classical. Classical monocytes are thought to readily convert to non-classical monocytes with exogenous cues. Studies on bulk monocyte populations have shown that monocytes acquire functional features dependent on physiological needs supporting a prevailing model that monocytes are highly plastic. We adapted a system for inducible clonal expansion of mouse granulocyte-monocyte progenitor (GMP) capable of differentiating into mature myeloid cells to address at a clonal level the issues of monocyte heterogeneity, plasticity, and whether changes in monocyte functional groups are due to induction or selection, Using inducible HoxB8-ER, large numbers of primary self-renewing GMP can undergo progressive maturation to fully functional granulocytes or monocytes upon removal of estrogen. The resulting GMP clones could then be characterized molecularly and immunophenotypically in correlation with the specialized functions of their descendent monocytes (Figure 1A). Four GMP differentiation trajectories that yield functionally distinct monocytes were defined (Figures 1B and 1C). Notably the functional monocyte groups were evident at the GMP level based on unsupervised clustering of chromatin configuration data (Figure 1D). GMP bore epigenetic scripting of the potential of their descendent monocytes and this fate had little flexibility once differentiation had begun. Testing cells under in vitro and in vivo homeostasis and stress conditions revealed that the cells maintain their differentiation path and do not transition from one state to another (Figures 1E and 1F). These data imply a model whereby monocyte stimulus-specific selection may occur and may contribute to an innate immune memory that resembles adaptive immune memory. Figure 1 Figure 1. Disclosures Sykes: Keros Therapeutics: Consultancy; SAFI Biosolutions: Consultancy, Current equity holder in publicly-traded company; Clear Creek Bio: Current equity holder in publicly-traded company. Scadden: Magenta Therapeutics: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Clear Creek Bio: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; LifeVaultBio: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Editas Medicines: Membership on an entity's Board of Directors or advisory committees; Fate Therapeutics: Current holder of individual stocks in a privately-held company; Clear Creek Bio: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Dainippon Sumitomo Pharma: Other: Sponsored research; FOG Pharma:: Consultancy; Garuda Therapeutics: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; VCanBio: Consultancy; Inzen Therapeutics: Membership on an entity's Board of Directors or advisory committees.

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